Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity

PLoS ONE

Volumn 9, Issue 3, 2014, Pages

  Woo, Shih Lung ^a   Xu, Hang ^a   Li, Honggui ^a   Zhao, Yan ^a   Hu, Xiang ^a,b   Zhao, Jiajia ^a,b   Guo, Xin ^a   Guo, Ting ^a   Botchlett, Rachel ^a   Qi, Ting ^a   Pei, Ya ^a   Zheng, Juan ^a,b   Xu, Yiming ^c   An, Xiaofei ^d   Chen, Lulu ^b   Chen, Lili ^b   Li, Qifu ^e   Xiao, Xiaoqiu ^e   Huo, Yuqing ^c,d   Wu, Chaodong ^a  

^a TEXAS A AND M UNIVERSITY   (United States)

^b HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY   (China)

^c MEDICAL COLLEGE OF GEORGIA   (United States)

^d PEKING UNIVERSITY   (China)

^e CHONGQING MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INTERLEUKIN 1BETA; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MESSENGER RNA; METFORMIN; STRESS ACTIVATED PROTEIN KINASE 1; TRANSCRIPTION FACTOR RELA; TUMOR NECROSIS FACTOR ALPHA; ANTIDIABETIC AGENT; GLUCOSE; MITOGEN ACTIVATED PROTEIN KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; C57BL 6 MOUSE; CONTROLLED STUDY; FEMALE; GLUCOSE TOLERANCE; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID DIET; LIPID STORAGE; LIVER CELL; LIVER WEIGHT; MACROPHAGE ACTIVATION; MALE; MOUSE; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; PROTEIN PHOSPHORYLATION; ADIPOSE TISSUE; ANIMAL; DISEASE MODEL; DRUG EFFECTS; FATTY LIVER; GLUCOSE INTOLERANCE; IMMUNOLOGY; INFLAMMATION; MACROPHAGE; METABOLISM; PATHOLOGY; PHOSPHORYLATION;

ADIPOSE TISSUE; ANIMALS; DIET, HIGH-FAT; DISEASE MODELS, ANIMAL; FATTY LIVER; GLUCOSE; GLUCOSE INTOLERANCE; HEPATOCYTES; HYPOGLYCEMIC AGENTS; INFLAMMATION; INSULIN RESISTANCE; MACROPHAGE ACTIVATION; MACROPHAGES; MALE; METFORMIN; MICE; MITOGEN-ACTIVATED PROTEIN KINASES; OBESITY; PHOSPHORYLATION;

EID: 84898619692     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0091111     Document Type: Article

References (48)

1. Tilg H, Kaser A (2005) Treatment strategies in nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2: 148-155. (Pubitemid 40812514)
2. Tilg H, Moschen AR (2010) Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis. Hepatology 52: 1836-1846.
3. Targher G, Bertolini L, Poli F, Rodella S, Scala L, et al. (2005) Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 54: 3541-3546. (Pubitemid 43334347)
4. Farrell GC, Larter CZ (2006) Nonalcoholic fatty liver disease: From steatosis to cirrhosis. Hepatology 43: S99-S112.
5. Shimomura I, Bashmakov Y, Horton JD (1999) Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem 274: 30028-30032.
6. Browning JD, Horton JD (2004) Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114: 147-152. (Pubitemid 39071617)
7. Odegaard JI, Ricardo-Gonzalez RR, Red Eagle A, Vats D, Morel CR, et al. (2008) Alternative M2 activation of Kupffer cells by PPARd ameliorates obesityinduced insulin resistance. Cell Metab 7: 496-507. (Pubitemid 351729205)
8. Joshi-Barve S, Barve SS, Amancherla K, Gobejishvili L, Hill D, et al. (2007) Palmitic acid induces production of proinflammatory cytokine interleukin-8 from hepatocytes. Hepatology 46: 823-830. (Pubitemid 47436129)
9. Nakamura S, Takamura T, Matsuzawa-Nagata N, Takayama H, Misu H, et al. (2009) Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. J Biol Chem 284: 14809-14818.
10. Kamei N, Tobe K, Suzuki R, Ohsugi M, Watanabe T, et al. (2006) Overexpression of monocyte chemoattractant protein-1 in adipose tissues causes macrophage recruitment and insulin resistance. J Biol Chem 281: 26602-26614. (Pubitemid 44401869)
11. Kelley DE, McKolanis TM, Hegazi RAF, Kuller LH, Kalhan SC (2003) Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. Am J Physiol Endocrinol Metab 285: E906-916. (Pubitemid 37176440)
12. Schaffler A, Scholmerich J, Buchler C (2005) Mechanisms of Disease: adipocytokines and visceral adipose tissue -emerging role in nonalcoholic fatty liver disease. Nat Clin Pract Gastroenterol Hepatol 2: 273-280. (Pubitemid 40895403)
13. Marchesini G, Bianchi G, Tomassetti S, Zoli M, Melchionda N (2001) Metformin in non-alcoholic steatohepatitis. Lancet 358: 893-894. (Pubitemid 32900577)
14. Angulo P (2006) NAFLD, Obesity, and Bariatric Surgery. Gastroenterology 130: 1848-1852. (Pubitemid 43668867)
15. Neuschwander-Tetri BA (2010) NASH: Thiazolidinediones for NASH-one pill doesn't fix everything. Nat Rev Gastroenterol Hepatol 7: 243-244.
16. Perriello G, Misericordia P, Volpi E, Santucci A, Santucci C, et al. (1994) Acute antihyperglycemic mechanisms of metformin in NIDDM. Evidence for suppression of lipid oxidation and hepatic glucose production. Diabetes 43: 920-928.
17. Stumvoll M, Nurjhan N, Perriello G, Dailey G, Gerich JE (1995) Metabolic effects of metformin in non-insulin dependant diabetes mellitus. N Engl J Med 333: 550-554.
18. Song S, Andrikopoulos S, Filippis C, Thorburn AW, Khan D, et al. (2001) Mechanism of fat-induced hepatic gluconeogenesis: effect of metformin. Am J Physiol Endocrinol Metab 281: E275-282.
19. Heishi M, Ichihara J, Teramoto R, Itakura Y, Hayashi K, et al. (2006) Global gene expression analysis in liver of obese diabetic db/db mice treated with metformin. Diabetologia 49: 1647-1655. (Pubitemid 43848102)
20. Zang M, Zuccollo A, Hou X, Nagata D, Walsh K, et al. (2004) AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulinresistant human HepG2 cells. J Biol Chem 279: 47898-47905. (Pubitemid 39540941)
21. He L, Sabet A, Djedjos S, Miller R, Sun X, et al. (2009) Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell 137: 635-646.
22. Foretz M, Hébrard S, Leclerc J, Zarrinpashneh E, Soty M, et al. (2010) Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. J Clin Invest 120: 2355-2369.
23. Kita Y, Takamura T, Misu H, Ota T, Kurita S, et al. (2012) Metformin prevents and reverses inflammation in a non-diabetic mouse model of nonalcoholic steatohepatitis. PLoS ONE 7: e43056.
24. Lee KM, Yang S-J, Kim YD, Choi YD, Nam JH, et al. (2013) Disruption of the cereblon gene enhances hepatic AMPK activity and prevents high-fat dietinduced obesity and insulin resistance in mice. Diabetes 62: 1855-1864.
25. Tajima K, Nakamura A, Shirakawa J, Togashi Y, Orime K, et al. (2013) Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice. Am J Physiol Endocrinol Metab 305: E987-E998.
26. Kim S, Sohn I, Ahn J-I, Lee K-H, Lee YS, et al. (2004) Hepatic gene expression profiles in a long-term high-fat diet-induced obesity mouse model. Gene 340: 99-109. (Pubitemid 39360236)
27. Kim S, Sohn I, Lee YS, Lee YS (2005) Hepatic gene expression profiles are altered by genistein supplementation in mice with diet-induced obesity. J Nutr 135: 33-41. (Pubitemid 40094317)
28. Guo X, Li H, Xu H, Halim V, Zhang W, et al. (2012) Palmitoleate induces hepatic steatosis but suppresses liver inflammatory response in mice. PLoS ONE 7: e39286.
29. Chen Y, Mu P, He S, Tang X, Guo X, et al. (2013) Gly482Ser mutation impairs the effects of peroxisome proliferator-activated receptor c coactivator-1a on decreasing fat deposition and stimulating phosphoenolpyruvate carboxykinase expression in hepatocytes. Nutr Res 33: 332-339.
30. Deng Z, Liu Y, Cunren Liu C, Xiang X, Wang J, et al. (2009) Immature myeloid cells induced by a high-fat diet contribute to liver inflammation. Hepatology 50: 1412-1420.
31. Bugianesi E, Gentilcore E, Manini R, Natale S, Vanni E, et al. (2005) A randomized controlled trial of metformin versus vitamin E or prescriptive diet in nonalcoholic fatty liver disease. Am J Gastroenterol 100: 1082-1090. (Pubitemid 40769045)
32. Li Y, Xu S, Mihaylova MM, Zheng B, Hou X, et al. (2011) AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metabolism 13: 376-388.
33. Zhang BB, Zhou G, Li C (2009) AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab 9: 407-416.
34. Huo Y, Guo X, Li H, Xu H, Halim V, et al. (2012) Targeted overexpression of inducible 6-phosphofructo-2-kinase in adipose tissue increases fat deposition but protects against diet-induced insulin resistance and inflammatory responses. J Biol Chem 287: 21492-21500.
35. Anthony J, Kelkar A, Wilankar C, Ranjith V, Bhumra SK, et al. (2013) Discovery of p1736, a novel antidiabetic compound that improves peripheral insulin sensitivity in mice models. PLoS ONE 8: e77946.
36. Shin N-R, Lee J-C, Lee H-Y, Kim M-S, Whon TW, et al. (2013) An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut Epub ahead of print.
37. Collier CA, Bruce CR, Smith AC, Lopaschuk G, Dyck DJ (2006) Metformin counters the insulin-induced suppression of fatty acid oxidation and stimulation of triacylglycerol storage in rodent skeletal muscle. Am J Physiol Endocrinol Metab 291: E182-E189. (Pubitemid 44035324)
38. Klein-Wieringa IR, Andersen SN, Kwekkeboom JC, Giera M, de Lange-Brokaar BJE, et al. (2013) Adipocytes modulate the phenotype of human macrophages through secreted lipids. J Immunol 191: 1356-1363.
39. Wu C, Okar DA, Newgard CB, Lange AJ (2001) Overexpression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in mouse liver lowers blood glucose by suppression of hepatic glucose production. J Clin Invest 107: 91-98. (Pubitemid 32047418)
40. Wu C, Kang JE, Peng L, Li H, Khan SA, et al. (2005) Enhancing hepatic glycolysis reduces obesity: Differential effects on lipogenesis depend on site of glycolytic modulation. Cell Metab 2: 131-140.
41. Wu C, Khan SA, Peng LJ, Li H, Camela S, et al. (2006) Perturbation of glucose flux in the liver by decreasing fructose-2,6-bisphosphate levels causes hepatic insulin resistance and hyperglycemia. Am J Physiol Endocrinol Metab 291: E536-543. (Pubitemid 44352259)
42. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, et al. (2005) Local and systemic insulin resistance resulting from hepatic activation of IKK-b and NFkB. Nat Med 11: 183-190. (Pubitemid 40321354)
43. Huo Y, Guo X, Li H, Wang H, Zhang W, et al. (2010) Disruption of inducible 6-phosphofructo-2-kinase ameliorates diet-induced adiposity but exacerbates systemic insulin resistance and adipose tissue inflammatory response. J Biol Chem 285: 3713-3721.
44. Guo X, Xu K, Zhang J, Li H, Zhang W, et al. (2010) Involvement of inducible 6-phosphofructo-2-kinase in the anti-diabetic effect of PPARc activation in mice. J Biol Chem 285: 23711-23720.
45. Stienstra R, Duval C, Keshtkar S, van der Laak J, Kersten S, et al. (2008) Peroxisome proliferator-activated receptor c activation promotes infiltration of alternatively activated macrophages into adipose tissue. J Biol Chem 283: 22620-22627.
46. Prieur X, Mok CYL, Velagapudi VR, Núnez V, Fuentes L, et al. (2011) Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice. Diabetes 60 797-809.
47. Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, Morel CR, Subramanian V, et al. (2007) Macrophage-specific PPARc controls alternative activation and improves insulin resistance. Nature 447: 1116-1120. (Pubitemid 47014427)
48. Guo X, Li H, Xu H, Halim V, Thomas LN, et al. (2013) Disruption of inducible 6-phosphofructo-2-kinase impairs the suppressive effect of PPARc activation on diet-induced intestine inflammatory response. J Nutr Biochem 24: 770-775.